Does blocking IRE1/JNK calm ferroptosis in AKI?
In I/R mice and H/R HK-2 cells, IRE1/JNK activation tracked with ferroptosis; inhibiting the pathway improved BUN/creatinine and ferroptosis markers.
Source
Inhibition of the IRE1/JNK pathway in renal tubular epithelial cells attenuates ferroptosis in acute kidney injury
Study at a glance
- Design
- Animal / in-vitro — Mouse renal ischemia–reperfusion plus hypoxia/reoxygenation in HK-2 cells; IRE1/JNK and ferroptosis
- N
- Animal and cell experiments; no single human N
- Population
- Mice with renal ischemia–reperfusion injury and cultured human tubular epithelial cells
- Outcome
- Ferroptosis in acute kidney injury after IRE1/JNK pathway inhibition
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Inspect source passages
Does blocking IRE1/JNK calm ferroptosis in AKI?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
144 male C57BL/6J mice were used for the I/R model.
One hundred and forty-four healthy male, eight-weeks-old C57BL/6J mice (20–25 g in mass) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.
Ferrostatin-1 was given at 0.8 mg/kg before I/R.
Ferrostatin-1 (Fer-1, 0.8 mg/kg, Sigma-Aldrich Chemical, Darmstadt, Germany), a ferroptosis inhibitor, was dissolved in DMSO and 0.9% NaCl and injected into mice via tail vein at 24 h before I/R.
What they did
Modeled AKI with renal ischemia-reperfusion in 144 mice and hypoxia/reoxygenation in HK-2 cells, then inhibited IRE1/JNK or ferroptosis (e.g., Fer-1) to test cross-talk.
What they found
I/R caused abnormal renal function, tubular injury, IRE1/JNK activation, and ferroptosis; H/R cells showed ROS and ferroptotic mitochondria. IRE1/JNK inhibition lowered BUN/creatinine/injury and shifted ferroptosis markers; ferroptosis inhibition also attenuated IRE1/JNK.
The limits
What it doesn't show
Mouse/cell protection is not yet a clinical AKI therapy; timing, off-target effects, and human translation remain open.
Key terms
- Ferroptosis
- Iron-dependent regulated cell death featuring lipid peroxidation and mitochondrial shrinkage.
- IRE1
- ER-stress sensor that can activate JNK signalling.
- JNK
- c-Jun NH2-terminal kinase pathway linked here to ferroptosis in AKI.
- I/R injury
- Ischemia-reperfusion damage used to model acute kidney injury in mice.
- HK-2 cells
- Human proximal tubular epithelial cell line used for H/R experiments.
- Ferrostatin-1
- Ferroptosis inhibitor (0.8 mg/kg in mice) used as a pharmacologic probe.
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Mouse N reported:
Common questions
Mouse N?
144 male C57BL/6J mice.
Main protective claim?
IRE1/JNK inhibition protects I/R kidneys by inhibiting ferroptosis.
In vitro injury model?
Hypoxia/reoxygenation in HK-2 cells.
Fer-1 dose cited?
0.8 mg/kg.